In recent years, nuclear fusion has been the focus of intense study. In yeast, nuclear envelope does not break down at any stage of the cell cycle or during mating. One essential factor for nuclear membrane fusion is Kar5p. The Kar5p protein is localized near the spindle pole body (SPB), where the fusion is initiated. Since it is the only known fusion factor associated with the SPB, it likely controls and/or promotes the fusion process. Consistent with this, I generated a number of kar5 alleles that are mislocalized and also, display a dominant-negative phenotype. Our current model is that Kar5p directs the other fusion factors specifically to the SPB. Interestingly, Kar5p is likely to function in mitotic cells. Since all the other fusion factors have roles in mitotic cells, it is reasonable to assume that Kar5p does the same. This research proposal outlines several molecular and genetic approaches to elucidate the role(s) of Kar5p in mating and mitotic cells. The function(s) of Kar5p are likely to be conserved since its homolog in fission yeast is also required for nuclear fusion. Furthermore, since homotypic membrane fusion occurs in all eukaryotic organisms, this study is of general interest for all fusion processes. Specific aims are (I) to test whether Kar5p is involved candidate pathways; (II) to identify its interacting factors; (III) to determine its mitotic function.